This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autoimmune responses do not occur spontaneously, even though humans carry autoreactive B and T cells, and these cells are educated to be tolerant to self-tissues. The mechanisms by which self tolerance is broken are the keys to the understanding of autoimmune diseases. It has been recently suggested that reactive oxygen species (ROS) are critical for the maintenance of T cell tolerance, the loss of which results in autoimmune diseases. A mutation in neutrophil cytosolic factor 1 (Ncf1, alias p47phox) leads to enhanced susceptibility to the spontaneous development of arthritis, and it is attributed to reduced oxidative burst (1, 2), implying that ROS have a beneficial role in controlling autoimmune responses. Our investigations will focus on multiple sclerosis (MS), an autoimmune disease in humans. We will use murine experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) as the disease model for MS in humans (3). The proposed studies will involve the use of EAE-susceptible, SJL and EAE-resistant B10.S strains of mice. This is a useful framework to determine the role of ROS in the genetic resistance to autoimmunity under defined conditions.